Bioprospecting the Antidiabetic and Antioxidant Properties of Dannetta tritapella Fruit: Using <i>In vitro</i>, ex vivo and <i>In silico</i> Confirmatory Model

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterized by hyperglycemia and oxidative stress. This study investigated the antidiabetic and antioxidant potential of D. tritapella fruit extracts using in vitro, ex vivo and in silico models. Methanol and ethylacetate extracts were prepared from dried D. tritapella fruits and evaluated for in vitro antioxidant and glucose uptake, alpha-amylase, glucosidase and trypsin inhibitory activities. The ability for the extract to prevent Fenton’s (Fe2+)- induced oxidative damage to the membrane liver was accessed. The Gas Chromatography-Mass Spectrometry (GC-MS) identified constituents of the extract were against alpha-amylase, glucosidase, lipase DPP-4 and trypsin in silico. Both D. tritapella extracts demonstrated concentration dependent αamylase, α-glucosidase and trypsin inhibitory while the ethylacetate extracts presented lower IC50 of 19.42 ± 0.15, 21.03 ± 1.05, 34.07 ± 1.1 µg/mL. The extracts inhibited 2,2-diphenyl-1-picrylhydrazyl (DPPH), superoxide anion (O2ˉ), hydroxyl anion (-OH) propagation and oxidatively reduced ferric ion to ferrous state in vitro. There was significant increase in the activities of catalase, superoxide dismutaseand reduced glutathione level and significant reduction in malondialdehyde (MDA) level in the liver homogenate contents co-treatment with both extract and Fenton’s reagents (p < 0.05). Molecular docking studies revealed 1,5-Bis[4-fluorophenyl]-2,5-dihydro-2,2-imethyl-1H-imidazo[4,5-b] phenaine 4 (C48) and stigmasterol (C44), 2-(Pentafluoropropionyl) oxybenzylidene acetophenone (C49), Furazan, 3-(dimethylaminomethylenamino)-4-(1,2,4-triazol-3-yl) (C46), and 2,3-diphenylcyclopropyl) methyl phenyl sulfoxide (C34) as the top docked compounds against five target proteins. Analysis of the molecular dynamic simulations trajectories revealed that the complexes formed remained stable over the course of the simulation. In conclusion, this study provides evidence that D. tritapella fruit extracts possess promising antidiabetic and antioxidant phytocompounds that support the prospect of D. tritapella fruits extracts as therapy for T2D